Search Results (76)

Background/Objectives: Extended-spectrum β-lactamase (ESBL)-producing Escherichia coli poses a significant global health challenge, as it leads to antimicrobial treatment failure and is associated with elevated mortality rates. The use of β-lactam/β-lactamase inhibitor combinations offers an alternative approach for combating ESBL-producing bacteria. Ceftriaxone (CRO) and sulbactam have been coadministered in the clinical settings; however, discrepancies in their pharmacokinetics raise concerns regarding the rationality of this combination. Methods: This study was designed to investigate the postβ-lactamase inhibitor effect (PLIE) under both static and dynamic conditions, with the aim of supporting the clinical application of this combination. Results: The minimum inhibitory concentration (MIC) of CRO/SBT (2:1 ratio) against E. coli NCTC 13353 was determined to be 32/16 μg/mL. The PLIEs were determined to be −1.26, −0.57, and 0.37 h at CRO/SBT concentrations ranging from 1/2 MIC to 2 MIC, respectively. The results of CRO concentration, β-lactamase activity, bla_CTX-M-15 expression, and cell morphology collectively support that SBT exerts PLIEs and protects against the antibacterial activity of CRO. In the dynamic hollow-fiber infection model, CRO monotherapy showed no inhibitory effect on E. coli, whereas CRO/SBT combination therapy rapidly eliminated SBT, achieved comparable bactericidal effects, prolonged CRO exposure, and maintained low β-lactamase activity levels. Conclusions: In conclusion, CRO/SBT exerts an inhibitory effect on enzyme-producing strains by being able to produce PLIE to maintain the inhibition of β-lactamase. Full article

Background/Objectives: Listeria monocytogenes is a foodborne pathogen of major public health concern due to its ability to invade host cells and cause severe illness. This study aimed to develop and validate a multi-tiered screening pipeline to identify Bacillus strains with probiotic potential against L. monocytogenes. Methods: A total of 26 Bacillus isolates were screened for antimicrobial activity, gastrointestinal resilience, and host cell adhesion. A fluorescence-based infection assay using mCherry-expressing HCT 116 cells was used to assess cytoprotection against L. monocytogenes NCTC 7973. Eight strains significantly improved host cell viability and were validated by quantification of intracellular CFU. Two top candidates were tested in a murine model of listeriosis. The genome of the lead strain was sequenced to evaluate safety and biosynthetic potential. Results: B. subtilis CECT 8266 completely inhibited intracellular replication of L. monocytogenes in HCT 116 cells, reducing bacterial recovery to undetectable levels. In vivo, it decreased splenic bacterial burden by approximately 6-fold. Genomic analysis revealed eight bacteriocin biosynthetic clusters and silent antibiotic resistance genes within predicted genomic islands, as determined by CARD and Alien Hunter analysis. The strain also demonstrated bile and acid tolerance, as well as strong adhesion to epithelial cells. Conclusions: The proposed pipeline enables efficient identification of probiotic Bacillus strains with intracellular protective activity. B. subtilis CECT 8266 is a promising candidate for translational applications in food safety or health due to its efficacy, resilience, and safety profile. Full article

Novel three-dimensional porous composites of alginate–pectin (A/P) with zinc- or manganese-substituted hydroxyapatites (A/P-ZnHA and A/P-MnHA) were synthesized via lyophilization and calcium cross-linking. Powder X-ray diffraction and infrared spectroscopy analyses confirmed single-phase apatite formation (crystallite sizes < 1 µm), with ZnHA exhibiting lattice contraction (*c*-axis: 6.881 Å vs. 6.893 Å for HA). Mechanical testing revealed tunable properties: pristine A/P sponges exhibited an elastic modulus of 4.7 MPa and a tensile strength of 0.10 MPa, reduced by 30–70% by HA incorporation due to increased porosity (pore sizes: 112 ± 18 µm in the case of MnHA vs. 148 ± 23 µm-ZnHA). Swelling capacity increased 2.3–2.8-fold (125–155% vs. 55% for A/P), governed by polysaccharide interactions. Scanning electron microscopy investigation showed microstructural evolution from layered A/P (<100 µm) to tridimensional architectures with embedded mineral particles. The A/P-MnHA composites demonstrated minimal cytotoxicity for the NCTC cells and good viability of dental pulp stem cells, while A/P-ZnHA caused ≈20% metabolic suppression, attributed to hydrolysis-induced acidification. Antibacterial assays highlighted A/P-MnHA′s broad-spectrum efficacy against Gram-positive (Bacillus atrophaeus) and Gram-negative (Pseudomonas protegens) strains, whereas A/P-ZnHA targeted only the Gram-positive strain. The developed composite sponges combine cytocompatibility and antimicrobial activity, potentially advancing osteoplastic materials for bone regeneration and infection control in orthopedic/dental applications. Full article

For decades, royal jelly achieved notoriety and became an ultra-rich ingredient with numerous pharmacological properties especially for its use in production of topical ointments and creams. A novel formulation enriched with 2% royal jelly has been developed and characterized. Rheological results highlight a gel-like behavior of the product in the packaging, as it does not flow from the costumer’s hand after application and behaves like a liquid, spreading evenly onto clean skin. A clear comparison in size distribution of pure and cream samples was noticed by dynamic light scattering analysis and completed further by Fourier transform infrared spectroscopy (FTIR-ATR) which showed off shift changes in the gel sample as compared to pure compounds. MTT assays were conducted in quintuplicate on murine fibroblasts cell line (NCTC L-929) for testing the biocompatibility of the product in the range of 50–1000 μg/mL over 24, 48 and 72 h. The designed formulation is typically intended to deliver active compounds to the skin surface and potentially into deeper layers. A molecular docking study was performed for binding mode prediction of P-gp protein residues with two ligands, quercetin and myricetin, in order to investigate their role in the internal modulation of drug transport across cell membranes within the skin. Full article

The screening of exopolysaccharides (EPS) produced by 52 isolates of endophytic and basidiomycete fungi was studied on two different media, PDB and PYGM. There were five isolates that could produce dried exopolysaccharide of more than 4 g/L (S. commune LF01962, LF01001, LF01581, Pycnoporus sp. MMCR00271.1, Pestalotiopsis sp. PP0005). The molecular weights of these exopolymers were found to be in the range of 2.5–500 kDa. These five exopolysaccharides, produced by five different fungal isolates, showed non-cytotoxic activity against NCTC clone 929 and HDFn cell lines. The selected fungal isolate of S. commune LF01962 was used for further optimization of different medium compositions affecting exopolysaccharide production using statistical methods. Among four conditions tested in the first step (xylose + peptone, glucose + (NH₄)₂HPO₄, fructose + peptone, and mannose + yeast extract), mannose + yeast extract resulted in the highest exopolysaccharide production of 5.10 ± 2.00 g/L. In the second step using Plackett–Burman design, the optimal medium for S. commune exopolysaccharide production was found to consist of 40 g/L glucose, 5 g/L mannose, 20 g/L (NH₄)₂HPO₄, 5 g/L yeast extract, 3 g/L monosodium glutamate, 0.5 g/L KH₂PO₄, 0.5 g/L K₂HPO₄, 0.2 g/L MgSO₄, 1 mL/L trace elements, and 3 mL/L vitamin solution, which resulted in 8.16 g/L exopolysaccharide production. Exopolysaccharide production in a 5 L bioreactor using small pellets as seed inoculum was found to produce 18.28 g/L exopolysaccharide. Full article

Background/Objectives. Psoriasis is a common chronic skin inflammatory disorder pathogenetically associated with genetic, environmental, and immunological factors. The hallmarks of psoriatic lesions include sustained inflammation related to alterations in the innate and adaptive immune response, uncontrolled keratinocyte proliferation, differentiation, and death, as well as dysregulated crosstalk between immune cells and keratinocytes. In search of novel therapeutic strategies based on the use of natural products and dietary components to combine to the available conventional and innovative therapeutics, we explored the anti-inflammatory, antioxidant, and immunomodulatory activities of Curcumin (CU)-based solid lipid nanoparticles (SLNs) carrying the omega-3 fatty acid linolenic acid (LNA) in an in vitro model of psoriasis that had been previously constructed and characterized by us. Methods. This in vitro model consists of differentiated in vitro THP-1 macrophages (Mφs) and NCTC-2544 keratinocytes exposed or not to conditioned medium (CM) from Mφs treated with the Toll-like receptor-7 ligand imiquimod (IMQ). Results. In Mφs, the treatment with CU-LNA-SLNs inhibited the IMQ-induced expression of proinflammatory cytokines (IL-23, IL-8, IL-6: 43%, 26.5% and 73.7% inhibition, respectively, vs IMQ-treated Mφs), as well as the hyperproliferative response (12.8% inhibition vs IMQ-treated Mφs) and the increase in cell death observed in keratinocytes treated with Mφ-derived CM (64.7% inhibition). Moreover, in the same conditions, CU-LNA-SLNs reverted to control levels of the increased keratinocyte expression of two markers of ferroptosis, a form of death recently involved in the pathogenesis of psoriasis (TFRC and MDA: 13.4% and 56.1% inhibition, respectively). Conclusions. These results suggest that CU-LNA-SLNs could inhibit psoriatic inflammation, as well as the hyperproliferation and death of keratinocytes in psoriatic lesions, and could be considered as a new possible therapeutic strategy for psoriasis to be further evaluated for the topic treatment of psoriatic skin in vivo. Full article

The aim of this study was to investigate the protective effects and potential mechanisms of Tetrahydrocurcumin (THC) on methionine–choline-deficient diet (MCD)-induced MASH in C57BL/6 mice by using multi-omics techniques. The C57BL/6 mice were fed with the MCD for 8 weeks to establish a MASH model, while THC (100 mg·kg⁻¹·d⁻¹) and obeticholic acid (6.5 mg·kg⁻¹·d⁻¹) were administered via gavage to the THC group and the positive control group, respectively. The biochemical indexes of the serum and liver were detected using kits. Liver tissue sections were taken to observe the pathomorphological changes. Serum lipid and bile acid contents were measured via LC-MS, and the changes in ileal intestinal flora were detected by 16S rDNA high-throughput sequencing technology. The results revealed that THC significantly attenuated oxidative stress and lipid accumulation in NCTC-1469 cells and relieved hepatic injury and oxidative stress, reduced hepatic TG content, and improved hepatic steatosis in mice. THC alleviated 34 lipid abnormalities caused by the MCD; increased the abundance and diversity of intestinal flora, the ratio of Firmicutes to Bacteroidota, and the abundance of the probiotic (Verrucomicrobiota, Christensenellaceae, Akkermansiaceae, Lachnospiraceae, Desulfovibrionaceae); and reduced the abundance of obesity-associated pathogenic flora such as Firmicutes. Bile acid analysis showed that THC administration reduced the levels of serum toxic bile acid 7-KDCA and CA. In addition, RT-qPCR studies showed that THC down-regulated the transcript levels of the hepatic lipogenesis-related genes Srebp1c, Acc1, Scd1, and Fas, and up-regulated the transcript levels of the hepatic bile acid secretion-related genes Mrp2 and Bsep. The above results suggest that THC may alleviate MCD-induced MASH by downregulating liver Srebp1c, Acc1, Scd1, and Fas levels to inhibit lipid synthesis, upregulating Mrp2 and Bsep levels to regulate serum toxic BA levels, up-regulating the abundance of intestinal probiotic flora, and down-regulating the abundance of intestinal harmful bacterial flora. The multi-omics findings from the above study identified potential new mechanisms by which THC alleviates MASH, providing new reference targets for the development of anti-MASH drugs. These results also offer a basis for screening clinical diagnostic biomarkers for MASH and provide new directions for personalized diagnosis and treatment. Full article

X-ray-induced photodynamic therapy (X-PDT) represents a promising new method of cancer treatment. A novel type of nanoscintillator based on cerium fluoride (CeF₃) nanoparticles (NPs) modified with flavin mononucleotide (FMN) has been proposed. A method for synthesizing CeF₃-FMN NPs has been developed, enabling the production of colloidal, spherical NPs with an approximate diameter of 100 nm, low polydispersity, and a high fluorescence quantum yield of 0.42. It has been demonstrated that CeF₃-FMN NPs exhibit pH-dependent radiation-induced redox activity when exposed to X-rays. This activity results in the generation of reactive oxygen species, which is associated with the scintillation properties of cerium and the transfer of electrons to FMN. The synthesized NPs have been demonstrated to exhibit minimal cytotoxicity towards normal cells (NCTC L929 fibroblasts) but are more toxic to tumor cells (epidermoid carcinoma A431). Concurrently, the synthesized NPs (CeF₃ and CeF₃-FMN NPs) demonstrate a pronounced selective radiosensitizing effect on tumor cells at concentrations of 10⁻⁷ and 10⁻³ M, resulting in a significant reduction in their clonogenic activity, increasing radiosensitivity for cancer cells by 1.9 times following X-ray irradiation at a dose of 3 to 6 Gy. In the context of normal cells, these nanoparticles serve the function of antioxidants, maintaining a high level of clonogenic activity. Functional nanoscintillators on the basis of cerium fluoride can be used as part of the latest technologies for the treatment of tumors within the framework of X-PDT. Full article

New haloaminopyrazole derivatives differing in the number of pyrazole nuclei 4a–f and 5a–e, respectively, were synthesized and characterized by ¹H-NMR, ¹³C-NMR, IR, UV-Vis, and elemental analysis. The single-crystal X-ray diffraction method was used to describe compounds 4a and 5d. When tested on normal NCTC fibroblasts in vitro, the newly synthesized derivatives were shown to be non-cytotoxic at a dosage of 25 μg/mL. Two compounds 4a and 5d showed a high degree of biocompatibility. From the two series of compounds tested on HEp-2 human cervical carcinoma cells, compound 5d showed a more pronounced antiproliferative effect. Gram-positive strains of Staphylococcus aureus ATCC25923, Enterococcus faecalis ATCC29212, Gram-negative strains of Pseudomonas aeruginosa ATCC27853, and strains of Escherichia coli ATCC25922 were used to test the newly synthesized compounds antibacterial and antibiofilm properties. Among the studied pyrazole compounds, 2 compounds 4a and 5a with fluorine content on the phenyl ring and 4 compounds 4b, 4e, 4f, and 5b with chlorine content on the phenyl ring were noted, which proved to be the most active compared with the two reference drugs, metronidazole and nitrofurantoin. The six compounds showed a broad spectrum of action against all four tested bacterial strains, the most active being compound 4b, with a chlorine atom in the “4” position of the phenyl nucleus and a MIC of 460 μg/mL. Compounds 4a and 5a showed the best antibiofilm activity against the bacterial strain Staphylococcus aureus ATCC25923, with an MBIC of 230 μg/mL. Full article

Objective. In this study, the biological effect of MTA Repair HP (Mineral Trioxide Aggregate Repair High Plasticity) and Biodentine have been tested on a stabilized fibroblast cell line NCTC clone 929. Materials and Methods. We assessed quantitative and qualitative parameters related to cytotoxic effect of the investigated products. The experimental period was 96 hours. Statistical analysis was performed with Kruskal-Wallis and Wilcoxon tests. Results. The detached cells test showed no statistically significant difference on cell culture for Biodentine and MTA Repair HP, while for the cellular density assay we found the same biological effect on the tested fibroblasts in the first 24 and 48 h, but a significant different cellular response for the investigated pulp capping materials for the next 48 h of the experiment. Conclusions. The results demonstrated that the materials presented a very low level of cytotoxicity. Biodentine showed in all parameters better biological effects than MTA Repair HP, expressed by lower and limited cellular damage and a higher cell density. Full article

Mesoporous titania nanoparticles (NPs) can be used for encapsulation polyphenols, with applications in the food industry, cosmetics, or biomedicine. TiO₂ NPs were synthesized using the sol-gel method combined with solvothermal treatment. TiO₂ NPs were characterized through X-ray diffraction, FTIR spectroscopy, the N₂ adsorption method, scanning and transmission electron microscopy, and thermal analysis. The sample prepared using Pluronic F127 presented a higher surface area and less agglomerated NPs than the samples synthesized with Pluronic P123. Grape marc (GM), a by-product from wine production, can be exploited for preparing extracts with good antioxidant properties. In this regard, we prepared hydroethanolic and ethanolic GM extracts from two cultivars, Feteasca Neagra (FN) and Pinot Noir. The extract components were determined by spectrometric analyses and HPLC. The extract with the highest radical scavenging activity, the hydroethanolic FN extract, was encapsulated in titania (FN@TiO₂) and compared with SBA-15 silica support. Both resulting materials showed biocompatibility on the NCTC fibroblast cell line in a 50–300 µg/mL concentration range after 48 h of incubation and even better radical scavenging potential than the free extract. Although titania has a lower capacity to host polyphenols than SBA-15, the FN@TiO₂ sample shows better cytocompatibility (up to 700 µmg/mL), and therefore, it could be used for skin-care products. Full article

Campylobacter jejuni is a common foodborne pathogen found in poultry that can cause severe life-threatening illnesses in humans. It is important to detect this pathogen in food to manage foodborne outbreaks. This study reports a novel impedimetric phage protein-based biosensor to detect C. jejuni NCTC 11168 at 100 CFU/mL concentrations using a genetically engineered receptor-binding phage protein, FlaGrab, as a bioreceptor. The electrochemical impedance spectroscopy (EIS) technique was employed to measure changes in resistance upon interaction with C. jejuni. The sensitivity of the phage protein-immobilized electrode was assessed using the various concentrations of C. jejuni NCTC 11168 ranging from 10²–10⁹ colony forming units (CFU)/mL). The change transfer resistance of the biosensor increased with increasing numbers of C. jejuni NCTC 11168 cells. The detection limit was determined to be approximately 10³ CFU/mL in the buffer and 10² CFU/mL in the ex vivo samples. Salmonella enterica subsp. enterica serotype Typhimurium-291RH and Listeria monocytogenes Scott A were used as nontarget bacterial cells to assess the specificity of the developed biosensor. Results showed that the developed biosensor was highly specific toward the target C. jejuni NCTC 11168, as no signal was observed for the nontarget bacterial cells. Full article

Starch is a common source of carbohydrates in aqua feed. High-starch diet can cause hepatic injury and lipid accumulation in fish. Mangiferin (MGF) can regulate lipid metabolism and protect the liver, but there is limited research on its effects in fish. In the present study, we investigated whether MGF could ameliorate high-starch-induced hepatic damage and lipid accumulation in channel catfish. The channel catfish (Ictalurus punctatus) were fed one of four experimental diets for eight weeks: a control diet (NCD), a high-starch diet (HCD), an HCD supplemented with 100 mg/kg MGF (100 MGF), and an HCD supplemented with 500 mg/kg MGF (500 MGF). The results demonstrated that the weight gain rate (WGR) (p = 0.031), specific growth rate (SGR) (p = 0.039), and feed conversion efficiency (FCE) (p = 0.040) of the 500 MGF group were significantly higher than those of the NCD group. MGF supplementation alleviated liver damage and improved antioxidant capacity (T-AOC) compared to those of the HCD group (p = 0.000). In addition, dietary MGF significantly reduced plasma glucose (GLU) (p = 0.000), triglyceride (TG) (p= 0.001), and low-density lipoprotein cholesterol (LDL) (p = 0.000) levels. It is noteworthy that MGF significantly reduced the plasma total cholesterol (TC) levels (p = 0.000) and liver TC levels (p = 0.005) of channel catfish. Dietary MGF improves cholesterol homeostasis by decreasing the expression of genes that are involved in cholesterol synthesis and transport (hmgcr, sqle, srebf2, sp1, and ldlr) and increasing the expression of genes that are involved in cholesterol catabolism (cyp7a1). Among them, the largest fold decrease in squalene epoxidase (sqle) expression levels was observed in the 100 MGF or 500 MGF groups compared with the HCD group, with a significant decrease of 3.64-fold or 2.20-fold (p = 0.008). And the 100 MGF or 500 MGF group had significantly decreased (by 1.67-fold or 1.94-fold) Sqle protein levels compared to those of the HCD group (p = 0.000). In primary channel catfish hepatocytes, MGF significantly down-regulated the expression of sqle (p = 0.030) and reduced cholesterol levels (p = 0.000). In NCTC 1469 cells, MGF significantly down-regulated the expression of sqle (p = 0.000) and reduced cholesterol levels (p = 0.024). In conclusion, MGF effectively inhibits sqle expression and reduces cholesterol accumulation. The current study shows how MGF supplementation regulates the metabolism and accumulation of cholesterol in channel catfish, providing a theoretical basis for the use of MGF as a dietary supplement in aquaculture. Full article

Campylobacter jejuni is the foodborne pathogen causing most gastrointestinal infections. Understanding its ability to form biofilms is crucial for devising effective control strategies in food processing environments. In this study, we investigated the growth dynamics and biofilm formation of C. jejuni NCTC 11168 in various culture media, including chicken juice (CJ), brain heart infusion (BHI), and Mueller Hinton (MH) broth. Our results demonstrated that C. jejuni exhibited a higher growth rate and enhanced biofilm formation in CJ and in 1:1 mixtures of CJ with BHI or MH broth compared to these measures in BHI or MH broth alone. Electron microscopy unveiled distinct morphological attributes of late-stage biofilm cells in CJ, including the presence of elongated spiral-shaped cells, thinner stretched structures compared to regular cells, and extended thread-like structures within the biofilms. Proteomic analysis identified significant alterations in protein expression profiles in C. jejuni biofilms, with a predominance of downregulated proteins associated with vital functions like metabolism, energy production, and amino acid and protein biosynthesis. Additionally, a significant proportion of proteins linked to biofilm formation, virulence, and iron uptake were suppressed. This shift toward a predominantly coccoid morphology echoed the reduced energy demands of these biofilm communities. Our study unlocks valuable insights into C. jejuni’s biofilm in CJ, demonstrating its adaptation and survival. Full article

Crystalline cerium(III) phosphate (CePO₄), cerium(IV) phosphates, and nanocrystalline ceria are considered to be promising components of sunscreen cosmetics. This paper reports on a study in which, for the first time, a quantitative comparative analysis was performed of the UV-shielding properties of CePO₄, Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5, and CePO₄/CeO₂ composites. Both the sun protection factor and protection factor against UV-A radiation of the materials were determined. Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5 was shown to have a sun protection factor of 2.9, which is comparable with that of nanocrystalline ceria and three times higher than the sun protection factor of CePO₄. Composites containing both cerium dioxide and CePO₄ demonstrated higher sun protection factors (up to 1.8) than individual CePO₄. When compared with the TiO₂ Aeroxide P25 reference sample, cerium(III) and cerium(IV) phosphates demonstrated negligible photocatalytic activity. A cytotoxicity analysis performed using two mammalian cell lines, hMSc and NCTC L929, showed that CePO₄, Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5, and nanocrystalline ceria were all non-toxic. The results of this comparative study indicate that cerium(IV) phosphate Ce(PO₄)(HPO₄)_0.5(H₂O)_0.5 is more advantageous for use in sunscreens than either cerium(III) phosphate or CePO₄/CeO₂ composites, due to its improved UV-shielding properties and low photocatalytic activity. Full article